GPR84
Description
The GPR84 (G protein-coupled receptor 84) is a protein-coding gene located on chromosome 12.
GPR84 (EX33) is a protein encoded by the GPR84 gene in humans. Discovered independently by two groups, GPR84 represents a unique GPCR subfamily. The GPR84 gene is located on chromosome 12q13.13 and is not interrupted by introns. The human and murine GPR84 proteins share 85% identity and are considered orthologs. GPR84 is expressed in various tissues, including brain, heart, muscle, colon, thymus, spleen, kidney, liver, intestine, placenta, lung, and leukocytes. Expression is particularly strong in the medulla and spinal cord.
GPR84 is a G protein-coupled receptor that is activated by medium-chain free fatty acids (FFAs) with carbon chain lengths of C9 to C14, such as capric acid (C10:0), undecanoic acid (C11:0), and lauric acid (C12:0). In immune cells, GPR84 acts as a pro-inflammatory receptor, promoting the production of inflammatory mediators like TNFα, IL-6, and IL-12B. It also triggers chemotaxis, bacterial adhesion, and phagocytosis in macrophages, and enhances NLRP3 inflammasome activation. GPR84 modulates neutrophil function by promoting chemotaxis, reactive oxygen species (ROS) production, and degranulation through the LYN-AKT/ERK pathway. It also interacts with the formyl peptide receptors FPR2 and FPR1 to regulate NADPH oxidase activity in neutrophils.
GPR84 is also known as EX33, GPCR4.
Associated Diseases
- isolated asymptomatic elevation of creatine phosphokinase
- plasma fibronectin deficiency
- pentosuria
- cancer
- myopathy due to calsequestrin and SERCA1 protein overload
- metabolic myopathy due to lactate transporter defect
